1
128 Abstracts/Lung Cancer I2 (1995) 113- I60 correlation with activity when compared logarithmically (t=O.879, p=O.O0002). Moreover, there was a significant relationship between enzyme activity and post-operative recurrence of lung cancer. In conclusion, thymidine kinase was found to be a useful marker of malignancy in lung cancer. ‘Daosforotiag growth factor-E, iohibita TCDD-iiduced eytuchrome P45OIAl expression in bumao lung caocer A549 cells Vogel C, Dohr 0, Abel J. Medical Inst. Environmental Hygiene, Heinrich-Heine-University, Department of Toxicology, Auf ‘m Hennekamp 50, 40225 Dusseldorf Arch Toxicol 1994;68:303-7. The effect of transforming growth factor-g, (TGF-g,) on the expression of cytochrome P450IAl (CYPIAl) was examined in 2.3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-treated human lung cancer A549 cells. Using the reverse transcription-polymerase chain reaction (RT- PCR) it was demonstrated that TGF6, inhibits CYPIAl expression in a dose dependent manner. Based on the inhibitory concentration 50 (IQ of about 5 pM it is suggested that TGF-8, has a physiological function in downregulation of this cytochrome. In the presence of cycloheximide, the effect of TGF-6, on CYPIAl mRNA disappeared. This finding indicates that protein synthesis may be required for the TGF-g, mediated response of CYFlAl. The possible mechanisms by which TGF-8, interacts with TCDD-responsive drug metabolizing enzymes are discnssed. Pathology Iououoohistuchemicai study of cathepsio B: Ptogoostic sigoificaoce in humao lung caocer Sukoh N, Abe S, Ogura S, Isobe H, Takekawa H, Inoue K, Kawakami Y. First Department of Medicine, School of Medicine, Hokkaido University, Kita IS. Nishi 7, Kilo-Ku, Sappoiv 060. Cancer 1994;74:46- 51. Bockground. The concentration of cysteine proteinase cathepsin B has been shown to be elevated in association with mahgnancy or metastatic potential of hmnan and rodent tumors, but its prognostic vahre for human lung cancer remains undetermined. Methods. Using a polyclonal antibody, immunohistochemical analyses ofcathepsin B were performed on pa&In embedded sections of tumors obtained surgically from 108 patients with non- small cell lung cancer (49 squamous cell carcinomas, 59 adenocarcinomas). The immunohistochemical expressions of cathepsin B in the tumors were compared with patient survival. Results. Higher grade. wcpression of cathepsin B was associated signiEcanUy with shorter survival in non-small cell lung cancer (F < O.Ol), in squamous all carcinoma (F < 0.05). and in adenocarcinoma (I’ cO.01). A similar result also was seen in Stage I non-small cell lung cancer (I’ < 0.05). Conclusions. The. authors concluded that the immnnOhistO- chemical staining pattern of cathepsin B may be a usetid predictor of survival for human lung cancer. Clinical assessment Basic aod ciioicai studies oo serum cytokeratio 19 frameot assay using centocorS CYFIIA 21-l kit in patients with lung caocer Hamase A, Sugimoto Y, Macda M, Kitani H, Fukuchi M. Department of Nuclear Medicine, Hyogo College of Medicine, Nishinomiya. Kaknigaku 1994;31:969-76. We evaluated the newly developed tumor marker assay kit, ‘Centocors CYFRA 21-l’. an immtmoradiometric assay (IRMA) kit for determining the serum cytokeratin 19 fragment using the sera of healthy subjects, patients with benign lung diseases and patients with lung cancer. The assay procedure is simple and based on the one-step IRMA system. Them were no problems in reproducibility, dilution test and recovery teat. The minimum detectable dose was 0.3 @ml. The antigen measmed by this kit was immunologically cross-reactive with tissue polypeptide antigen (TPA) and CYFRA 21-1 concentration was closely correlated with TPA concentration in the patient’s serum (r = 0.86, p <O.Ol). The cut-off value of serum CYFRA 21-1 based on the assay results of this kit was calculated to be 1.6 rig/ml from the receiver operating characteristic curve. Three of 47 healthy subjects (6.4%) and 9 of 30 patients with benign lung diseases (30.0%) showed a concentration over the cut-off value. By contrast, serum CYFRA 21-1 concentration was elevated in 31 of 50 patients with lung cancer (62.0%) 11 of 13 qoamons cell carcinoma patients (84.6%). 8 of 12 small cell carcinoma patients (66.7%) 4 of 7 large cell carcinoma patients (57.1%) and 8 of 18 adenocarcinoma patients (44.4%). In addition, the positive rate of serum CYFRA 21-1 in patients with lung cancer gradually increased with staging of the disease: 50.0% in stage I, 50.0% in stage II, 6 1.9% in stage III, and 76.9% in stage IV Thus, our results suggested that the Centoc& CYFRAZl-1 kit isausetidassay system for serumcytokeratin 19 fragment as a tumor marker in patients with lung cancer. Physical Atoess of patients with small ceil lung caocer Baracos YE, Urtasun RC, Humen DP, Haenuel RG. Department of Animal Science, Universily ofAlberto, Edmonton, Alta. T6G 2P5. Clin J Sport Med 1994;4:223-7. Muscular strength, endurance and cardiovascular fitness were evaluated in a group of patients (n = 11) previously treated for small cell lung cancer (SCLC). All SCLC patients were in complete remission and were 6 weeks posttherapy. Their results were compared to an age- and sex-matched group of cardiac patients who had undergone coronary artery bypass surgery (cardiac) 6-8 weeks prior, and a group of age- and sex-matched healthy controls. All subjects participated in a symptom- limited, graded exercise test on a cycle ergometer to determine peak aerobic power (VO,). Muscular strength and endurance of the upper and lower extremity were also assessed, with use of an Isokinetic dynamometer. Compared with both the healthy subjects and the cardiac patients, the SCLC patients demonstrated a signiticantIy lower exercise tolerance time, maximal power output, and peak V.Or @ < 0.05). Isokinetic testing of the lower extremity revealed lower peak torque, average torque, and absolute work values for the SCLC patients. Upper body muscular endurance was also significantIy reduced in the SCLC patients when compared with that for the healthy controls or the cardiac patients @ < 0.05). Current results suggest significantly diminished capacities in both the cardiorespiratory and muscular systems of SCLC patients who are 6 weeks posttherapy. Detection of lymph node metastases in lung caocer: Comparison of l”I-Aoti-CEA-Aoti-CA 19-Y immuoosciotigraphy versus computed tomography Boilleau G, Pujol J-L, Ychou M, Faurous P, Marty-Ane C, Michel F-B et al. Service des Maladies Respirotoirw, Hopital Arnaud de tWeneuw 34059 Montpeilier Cede%. Lung Cancer (heland) 1994;11:209-19. Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anticarcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of

Immunohistochemical study of cathepsin B: Prognostic significance in human lung cancer

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128 Abstracts/Lung Cancer I2 (1995) 113- I60

correlation with activity when compared logarithmically (t=O.879, p=O.O0002). Moreover, there was a significant relationship between enzyme activity and post-operative recurrence of lung cancer. In conclusion, thymidine kinase was found to be a useful marker of malignancy in lung cancer.

‘Daosforotiag growth factor-E, iohibita TCDD-iiduced eytuchrome P45OIAl expression in bumao lung caocer A549 cells Vogel C, Dohr 0, Abel J. Medical Inst. Environmental Hygiene, Heinrich-Heine-University, Department of Toxicology, Auf ‘m Hennekamp 50, 40225 Dusseldorf Arch Toxicol 1994;68:303-7. The effect of transforming growth factor-g, (TGF-g,) on the expression of cytochrome P450IAl (CYPIAl) was examined in 2.3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-treated human lung cancer A549 cells. Using the reverse transcription-polymerase chain reaction (RT- PCR) it was demonstrated that TGF6, inhibits CYPIAl expression in a dose dependent manner. Based on the inhibitory concentration 50 (IQ of about 5 pM it is suggested that TGF-8, has a physiological function in downregulation of this cytochrome. In the presence of cycloheximide, the effect of TGF-6, on CYPIAl mRNA disappeared. This finding indicates that protein synthesis may be required for the TGF-g, mediated response of CYFlAl. The possible mechanisms by which TGF-8, interacts with TCDD-responsive drug metabolizing enzymes are discnssed.

Pathology

Iououoohistuchemicai study of cathepsio B: Ptogoostic sigoificaoce in humao lung caocer Sukoh N, Abe S, Ogura S, Isobe H, Takekawa H, Inoue K, Kawakami Y. First Department of Medicine, School of Medicine, Hokkaido University, Kita IS. Nishi 7, Kilo-Ku, Sappoiv 060. Cancer 1994;74:46- 51. Bockground. The concentration of cysteine proteinase cathepsin B has been shown to be elevated in association with mahgnancy or metastatic potential of hmnan and rodent tumors, but its prognostic vahre for human lung cancer remains undetermined. Methods. Using a polyclonal antibody, immunohistochemical analyses ofcathepsin B were performed on pa&In embedded sections of tumors obtained surgically from 108 patients with non- small cell lung cancer (49 squamous cell carcinomas, 59 adenocarcinomas). The immunohistochemical expressions of cathepsin B in the tumors were compared with patient survival. Results. Higher grade. wcpression of cathepsin B was associated signiEcanUy with shorter survival in non-small cell lung cancer (F < O.Ol), in squamous all carcinoma (F < 0.05). and in adenocarcinoma (I’ cO.01). A similar result also was seen in Stage I non-small cell lung cancer (I’ < 0.05). Conclusions. The. authors concluded that the immnnOhistO- chemical staining pattern of cathepsin B may be a usetid predictor of survival for human lung cancer.

Clinical assessment

Basic aod ciioicai studies oo serum cytokeratio 19 frameot assay using centocorS CYFIIA 21-l kit in patients with lung caocer Hamase A, Sugimoto Y, Macda M, Kitani H, Fukuchi M. Department of Nuclear Medicine, Hyogo College of Medicine, Nishinomiya. Kaknigaku 1994;31:969-76.

We evaluated the newly developed tumor marker assay kit, ‘Centocors CYFRA 21-l’. an immtmoradiometric assay (IRMA) kit for determining the serum cytokeratin 19 fragment using the sera of healthy subjects, patients with benign lung diseases and patients with lung cancer. The assay procedure is simple and based on the one-step IRMA system. Them were no problems in reproducibility, dilution test and recovery teat. The minimum detectable dose was 0.3 @ml. The antigen measmed by this kit was immunologically cross-reactive with tissue polypeptide antigen (TPA) and CYFRA 21-1 concentration was closely correlated with TPA concentration in the patient’s serum (r = 0.86, p <O.Ol). The cut-off value of serum CYFRA 21-1 based on the assay results of this kit was calculated to be 1.6 rig/ml from the receiver operating characteristic curve. Three of 47 healthy subjects (6.4%) and 9 of 30 patients with benign lung diseases (30.0%) showed a concentration over the cut-off value. By contrast, serum CYFRA 21-1 concentration was elevated in 31 of 50 patients with lung cancer (62.0%) 11 of 13 qoamons cell carcinoma patients (84.6%). 8 of 12 small cell carcinoma patients (66.7%) 4 of 7 large cell carcinoma patients (57.1%) and 8 of 18 adenocarcinoma patients (44.4%). In addition, the positive rate of serum CYFRA 21-1 in patients with lung cancer gradually increased with staging of the disease: 50.0% in stage I, 50.0% in stage II, 6 1.9% in stage III, and 76.9% in stage IV Thus, our results suggested that the Centoc& CYFRAZl-1 kit isausetidassay system for serumcytokeratin 19 fragment as a tumor marker in patients with lung cancer.

Physical Atoess of patients with small ceil lung caocer Baracos YE, Urtasun RC, Humen DP, Haenuel RG. Department of Animal Science, Universily ofAlberto, Edmonton, Alta. T6G 2P5. Clin J Sport Med 1994;4:223-7. Muscular strength, endurance and cardiovascular fitness were evaluated in a group of patients (n = 11) previously treated for small cell lung cancer (SCLC). All SCLC patients were in complete remission and were 6 weeks posttherapy. Their results were compared to an age- and sex-matched group of cardiac patients who had undergone coronary artery bypass surgery (cardiac) 6-8 weeks prior, and a group of age- and sex-matched healthy controls. All subjects participated in a symptom- limited, graded exercise test on a cycle ergometer to determine peak aerobic power (VO,). Muscular strength and endurance of the upper and lower extremity were also assessed, with use of an Isokinetic dynamometer. Compared with both the healthy subjects and the cardiac patients, the SCLC patients demonstrated a signiticantIy lower exercise tolerance time, maximal power output, and peak V.Or @ < 0.05). Isokinetic testing of the lower extremity revealed lower peak torque, average torque, and absolute work values for the SCLC patients. Upper body muscular endurance was also significantIy reduced in the SCLC patients when compared with that for the healthy controls or the cardiac patients @ < 0.05). Current results suggest significantly diminished capacities in both the cardiorespiratory and muscular systems of SCLC patients who are 6 weeks posttherapy.

Detection of lymph node metastases in lung caocer: Comparison of l”I-Aoti-CEA-Aoti-CA 19-Y immuoosciotigraphy versus computed tomography Boilleau G, Pujol J-L, Ychou M, Faurous P, Marty-Ane C, Michel F-B et al. Service des Maladies Respirotoirw, Hopital Arnaud de tWeneuw 34059 Montpeilier Cede%. Lung Cancer (heland) 1994;11:209-19. Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anticarcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of